Search results for: drug therapy problems

Authors: H. Yousefnia, R. Enayati, M. Hosntalab, S. Zolghadri, A. Bahrami-Samani

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Bone metastases occur in many cases at an early stage of the tumour disease, however their symptoms are recognized rather late. The aim of this study was the preparation of 153Sm-(4-{[bis-(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl) 1,4,7,10-tetraazacyclododec-1-yl) acetic acid (BPAMD) for bone pain palliation therapy. 153Sm was produced at Tehran research reactor via 152Sm(n,γ)153Sm reaction. 200 µl of 1mg/ml BPAMD solution was added to the vial containing 1 mCi 153Sm and the mixture was heated up to 90 0C for 1 h. The radiochemical purity of the complex was measured by ITLC method. The final solution with radiochemical purity of more than 95% was injected to BALB mice and bio distribution was determined up to 48 h. SPECT images were acquired after 2 and 24 h post injection. While high bone uptake was confirmed by both the bio distribution studies and SPECT imaging, accumulation in other organs was approximately negligible. The results show that 153Sm-BPAMD can be used as an excellent tracer for bone pain palliation therapy.

Keywords: bone metastases, BPAMD, 153Sm, radiotherapy

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Authors: Nunuy Nuraeni, Vera Amalia Lestari, Atri Laranova, Viena Nissa Mien Fadhillah, Mutia, Muhammad Ikhlas Abdian Putra

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Introduction: Obesity is a common disease with high prevalence especially in developing countries including Indonesia. The obesitygenic lifestyle such as excessive intake of food, sedentary lifestyle is the major environmental etiologies of obesity. Obesity is also as one of burden disease with high morbidity due to its complication, such as diabetes mellitus and hypertension. The objective of this literature review is to know how the Epigallocathecin-3-Gallate of Green tea or Camellia sinensis effect as anti-obesity agent and reduce the complication of obesity. Material and Methods: This study based on the secondary data analysis complemented by primary data collection from several journal and textbook. We identified the effect of Epigallocathecin-3-Gallate of Green tea or Camellia sinensis as adjuvant therapy for management obesity and to prevent the complications of obesity. Results: Based on the result, Green tea or Camellia sinensis contain Epigallocathecin-3-Gallate (EGCG) that has anti-obesity effect such as induce apoptosis, inhibit adipogenesis, increasing lipolytic activity, increasing fat oxidation and thermogenesis. Discussion: EGCG are naturally distributed in green tea, that contains a biological activity that has a potential effect to treat obesity. Conclusion: EGCG are capable to treat obesity. By consuming EGCG can prevent obesity in normal health person and prevent complication in patient with obesity.

Keywords: adjuvant therapy, anti-obesity effect, complication, epigallocathecin-3-gallate, obesity

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Authors: Santhosh A. K.

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This work presents an efficient monolithic finite element strategy for solving thermo-fluid-structure interaction problems involving compressible fluids and linear-elastic structure. This formulation uses displacement variables for structure and velocity variables for the fluid, with no additional variables required to ensure traction, velocity, temperature, and heat flux continuity at the fluid-structure interface. Rate of convergence in each time step is quadratic, which is achieved in this formulation by deriving an exact tangent stiffness matrix. The robustness and good performance of the method is ascertained by applying the proposed strategy on a wide spectrum of problems taken from the literature pertaining to steady, transient, two dimensional, axisymmetric, and three dimensional fluid flow and conjugate heat transfer. It is shown that the current formulation gives excellent results on all the case studies conducted, which includes problems involving compressibility effects as well as problems where fluid can be treated as incompressible.

Keywords: linear thermoelasticity, compressible flow, conjugate heat transfer, monolithic FEM

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Authors: Yaowaporn Sangsen, Kittisak Likhitwitayawuid, Boonchoo Sritularak, Kamonthip Wiwattanawongsa, Ruedeekorn Wiwattanapatapee

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Novel solid lipid nanoparticles (SLNs) were developed to improve oral bioavailability of oxyresveratrol (OXY). The SLNs were prepared by a high speed homogenization technique, at an effective speed and time, using Compritol® 888 ATO (5% w/w) as the solid lipid. The appropriate weight proportions (0.3% w/w) of OXY affected the physicochemical properties of blank SLNs. The effects of surfactant types on the properties of the formulations such as particle size and entrapment efficacy were also investigated. Conclusively, Tween 80 combined with soy lecithin was the most appropriate surfactant to stabilize OXY-loaded SLNs. The mean particle size of the optimized formulation was 134.40 ± 0.57 nm. In vitro drug release study, the selected S2 formulation showed a retarded release profile for OXY with no initial burst release compared to OXY suspension in the simulated gastrointestinal fluids. Therefore, these SLNs could provide a suitable system to develop for the oral OXY delivery.

Keywords: solid lipid nanoparticles, physicochemical properties, in vitro drug release, oxyresveratrol

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Authors: G. Battistoni, F. Collamati, E. De Lucia, R. Faccini, C. Mancini-Terracciano, M. Marafini, I. Mattei, S. Muraro, V. Patera, A. Sarti, A. Sciubba, E. Solfaroli Camillocci, M. Toppi, G. Traini, S. M. Valle, C. Voena

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Accelerated charged particles, mainly protons and carbon ions, are presently used in Particle Therapy (PT) to treat solid tumors. The precision of PT exploiting the charged particle high localized dose deposition in tissues and biological effectiveness in killing cancer cells demands for an online dose monitoring technique, crucial to improve the quality assurance of treatments: possible patient mis-positionings and biological changes with respect to the CT scan could negatively affect the therapy outcome. In PT the beam range confined in the irradiated target can be monitored thanks to the secondary radiation produced by the interaction of the projectiles with the patient tissue. The Dose Profiler (DP) is a novel device designed to track charged secondary particles and reconstruct their longitudinal emission distribution, correlated to the Bragg peak position. The feasibility of this approach has been demonstrated by dedicated experimental measurements. The DP has been developed in the framework of the INSIDE project, MIUR, INFN and Centro Fermi, Museo Storico della Fisica e Centro Studi e Ricerche 'E. Fermi', Roma, Italy and will be tested at the Proton Therapy center of Trento (Italy) within the end of 2017. The DP combines a tracker, made of six layers of two-view scintillating fibers with square cross section (0.5 x 0.5 mm2) with two layers of two-view scintillating bars (section 12.0 x 0.6 mm2). The electronic readout is performed by silicon photomultipliers. The sensitive area of the tracking planes is 20 x 20 cm2. To optimize the detector layout, a Monte Carlo (MC) simulation based on the FLUKA code has been developed. The complete DP geometry and the track reconstruction code have been fully implemented in the MC. In this contribution, the DP hardware will be described. The expected detector performance computed using a dedicated simulation of a 220 MeV/u carbon ion beam impinging on a PMMA target will be presented, and the result will be discussed in the standard clinical application framework. A possible procedure for real-time beam range monitoring is proposed, following the expectations in actual clinical operation.

Keywords: online range monitoring, particle therapy, quality assurance, tracking detector

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Authors: Waheed Zahra, Mohamed El-Beltagy, Ashraf El Mhlawy, Reda Elkhadrawy

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In this paper, we consider singular perturbation reaction-diffusion boundary value problems, which contain a small uncertain perturbation parameter. To solve these problems, we propose a numerical method which is based on an exponential spline and Shishkin mesh discretization. While interval analysis principle is used to deal with the uncertain parameter, sensitivity analysis has been conducted using different methods. Numerical results are provided to show the applicability and efficiency of our method, which is ε-uniform convergence of almost second order.

Keywords: singular perturbation problem, shishkin mesh, two small parameters, exponential spline, interval analysis, sensitivity analysis

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Authors: Bakur Gulua

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In this work, we consider some boundary value problems for the plate. The plate is the elastic material with voids. The state of plate equilibrium is described by the system of differential equations that is derived from three-dimensional equations of equilibrium of an elastic material with voids (Cowin-Nunziato model) by Vekua's reduction method. Its general solution is represented by means of analytic functions of a complex variable and solutions of Helmholtz equations. The problem is solved analytically by the method of the theory of functions of a complex variable.

Keywords: the elastic material with voids, boundary value problems, Vekua's reduction method, a complex variable

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Authors: Mustafa Gulsen, Mitat Koz

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The aim of this study is to investigate the effect of lumbar stabilisation and proprioceptive neuromuscular facilitation (PNF) training on muscle strength and muscle endurance. The participants were 64 between the ages of 15-69 (53.04 ± 14.59), who were graded protrusion and bulging lumbar herniation according to 'Macnab Classification'. The participants were divided into four groups as each group had 16 participants: lumbar stabilitation training, PNF training, physical therapy and control groups. Sociodemographic features were recorded. Then their muscle strength tests (by isokinetic dynamometer (Cybex 770 Norm Lumex Inc, Ronkonkoma, NY, USA) were recorded. Before and after applications; visual analogue scale (VAS), Oswestry Disability İndex were applied by a physical therapist. The participants in lumbar stabilisation group performed 45 minutes, 5 days in a week for 4 weeks strength training with a physical therapist observation. The participants in PNF group performed 5 days in a week for 4 weeks with pelvic patterns of PNF by a physiotherapist. The participants in physical therapy group underwent Hotpack, Tens and Ultrasound therapy 5 days in a week for 4 weeks. The participants in control group didn’t take any training programme. After 4 weeks, the evaluations were repeated. There were significant increases in muscle strength and muscle endurance in lumbar stabilization training group. Also in pain intensity at rest and during activity in this group and in Oswestry disability index of patients, there were significant improvements (p < 0.05). In PNF training group likewise, there were significant improvements in muscle strength, muscle endurance, pain intensity at rest and with activity and in Oswestry disability index (p < 0.05). But improvements in the Lumbar Stabilization group was better than PNF Group. We found significant differences only in pain intensity at rest and with activity and in Oswestry disability index (p < 0.05). in the patients in Physical Therapy group. We think that appropriate physiotherapy and rehabilitation program which will be prepared for patients, to protect the waist circumference of patients with low muscle strength and low muscle endurance will increase muscle strength and muscle endurance. And it is expected that will reduce pain and will provide advances toward correcting functional disability of the patients.

Keywords: disc herniation, endurance, lumbar stabilitation exercises, PNF, strength

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Authors: Zakia Belhadj, Bing He, Hua Zhang, Xueqing Wang, Wenbing Dai, Qiang Zhang

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Mononuclear phagocyte system (MPS) forms an abominable obstacle hampering the tumor delivery efficiency of nanoparticles. Passively targeted nanocarriers have received clinical approval over the past 20 years. However, none of the actively targeted nanocarriers have entered clinical trials. Thus it is important to endue effective targeting ability to actively targeted approaches by overcoming biological barriers to nanoparticle drug delivery. Here, it presents that an Esomeprazole-based preconditioning strategy for regulating nanocarrier-MPS interaction to substantially prolong circulation time and enhance tumor targeting of nanoparticles. In vitro, the clinically approved proton pump inhibitor Esomeprazole “ESO” was demonstrated to reduce interactions between macrophages and subsequently injected targeted vesicles by interfering with their lysosomal trafficking. Of note, in vivo studies demonstrated that ESO pretreatment greatly decreased the liver and spleen uptake of c(RGDm7)-modified vesicles, highly enhanced their tumor accumulation, thereby provided superior therapeutic efficacy of c(RGDm7)-modified vesicles co-loaded with Doxorubicin (DOX) and Gefitinib (GE). This MPS-preconditioning strategy using ESO provides deeper insights into regulating nanoparticles interaction with the phagocytic system and enhancing their cancer cells' accessibility for anticancer therapy.

Keywords: esomeprazole (ESO), mononuclear phagocyte system (MPS), preconditioning strategy, targeted lipid vesicles

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Authors: Marwa T. Badawy, Alaa F. Bakr, Nesrine Hegazi, Mohamed A. Farag, Ahmed Abdellatif

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Diabetes Mellitus (DM) is a chronic disease affecting a large population worldwide. Africa is rich in native medicinal plants with myriad health benefits, though less explored towards the development of specific drug therapy as in diabetes. This study aims to determine the in vivo antidiabetic potential of the well-reported and traditionally used fruits of Baobab (Adansonia digitata L.) using STZ induced diabetic model. The in-vitro cytotoxic and antioxidant properties were examined using MTT assay on L-929 fibroblast cells and DPPH antioxidant assays, respectively. The extract showed minimal cytotoxicity with an IC50 value of 105.7 µg/mL. Histopathological and immunohistochemical investigations showed the hepatoprotective and the renoprotective effects of A. digitata fruits’ extract, implying its protective effects against diabetes complications. These findings were further supported by biochemical assays, which showed that i.p., injection of a low dose (150 mg/kg) of A. digitata twice a week lowered the fasting blood glucose levels, lipid profile, hepatic and renal markers. For a comprehensive overview of extract metabolites composition, ultrahigh performance (UHPLC) analysis coupled to high-resolution tandem mass spectrometry (HRMS/MS) in synchronization with molecular networks led to the annotation of 77 metabolites, among which 50% are reported for the first time in A. digitata fruits.

Keywords: adansonia digital, diabetes mellitus, metabolomics, streptozotocin, Sprague, dawley rats

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Authors: Web Huei Chou, Li Yi Chun, Wenwe Yu, Han Teng Weng, H. Yuan, T. Yang

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The prevalence of dementia is estimated to rise to 78 million by 2030 and 139 million by 2050. Among those affected, Alzheimer's disease is the most common form of dementia, contributing to 60–70% of cases. Addressing this growing challenge is crucial, especially considering the impact on older individuals and their caregivers. To reduce the behavioral and psychological symptoms of dementia, people with dementia use a variety of pharmaceutical and non-pharmacological treatments, and some studies have found the use of non-pharmacological interventions. Treatment of depression, cognitive function, and social activities has potential benefits. Butler developed reminiscence therapy as a method of treating dementia. Through ‘life review,’ individuals can recall their past events, activities, and experiences, which can reduce the depression of the elderly and improve their Quality of life to help give meaning to their lives and help them live independently. The life review process uses a variety of memory triggers, such as household items, past objects, photos, and music, and can be conducted collectively or individually and structured or unstructured. However, despite the advantages of nostalgia therapy, past research has always pointed out that current research lacks rigorous experimental evaluation and cannot describe clear research results and generalizability. Therefore, this study aims to study physiological sensing experiments to find a feasible experimental and verification method to provide clearer design and design specifications for reminiscence therapy and to provide a more widespread application for healthy aging. This study is an ongoing research project, a collaboration between the School of Design at Yunlin University of Science and Technology in Taiwan and the Department of Medical Engineering at Chiba University in Japan. We use traditional rice dishes from Taiwan and Japan as nostalgic content to construct a narrative structure for the elderly in the two countries respectively for life review activities, providing an easy-to-carry nostalgic therapy game with an intuitive interactive design. This experiment is expected to be completed in 36 months. The design team constructed and designed the game after conducting literary and historical data surveys and interviews with elders to confirm the nostalgic historical data in Taiwan and Japan. The Japanese team planned the Electrodermal Activity (EDA) and Blood Volume Pulse (BVP) experimental environments and Data calculation model, and then after conducting experiments on elderly people in two places, the research results were analyzed and discussed together. The research has completed the first 24 months of pre-study, design work, and pre-study and has entered the project acceptance stage.

Keywords: reminiscence therapy, aging health, design research, life review

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Authors: Vijaya Kumar, Vidayasagar Pagilla, Abraham Joshua, Rakshith Kedambadi, Prasanna Mithra

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Background: Post stroke rehabilitation are aimed to accelerate for optimal sensorimotor recovery, functional gain and to reduce long-term dependency. Intensive physical therapy interventions can enhance this recovery as experience-dependent neural plastic changes either directly act at cortical neural networks or at distal peripheral level (muscular components). Neuromuscular Electrical Stimulation (NMES), a traditional bottom-up approach, mirror therapy (MT), a relatively new top down approach have found to be an effective adjuvant treatment methods for lower extremity motor and functional recovery in stroke rehabilitation. However there is a scarcity of evidence to compare their therapeutic gain in stroke recovery.Aim: To compare the efficacy of neuromuscular electrical stimulation (NMES) and mirror therapy (MT) in very early phase of post stroke rehabilitation addressed to lower extremity motor recovery and balance. Design: observer blinded Randomized Clinical Trial. Setting: Neurorehabilitation Unit, Department of Physical Therapy, Tertiary Care Hospitals. Subjects: 32 acute stroke subjects with first episode of unilateral stroke with hemiparesis, referred for rehabilitation (onset < 3 weeks), Brunnstorm lower extremity recovery stages ≥3 and MMSE score more than 24 were randomized into two group [Group A-NMES and Group B-MT]. Interventions: Both the groups received eclectic approach to remediate lower extremity recovery which includes treatment components of Roods, Bobath and Motor learning approaches for 30 minutes a day for 6 days. Following which Group A (N=16) received 30 minutes of surface NMES training for six major paretic muscle groups (gluteus maximus and medius,quadriceps, hamstrings, tibialis anterior and gastrocnemius). Group B (N=16) was administered with 30 minutes of mirror therapy sessions to facilitate lower extremity motor recovery. Outcome measures: Lower extremity motor recovery, balance and activities of daily life (ADLs) were measured by Fugyl Meyer Assessment (FMA-LE), Berg Balance Scale (BBS), Barthel Index (BI) before and after intervention. Results: Pre Post analysis of either group across the time revealed statistically significant improvement (p < 0.001) for all the outcome variables for the either group. All parameters of NMES had greater change scores compared to MT group as follows: FMA-LE (25.12±3.01 vs. 23.31±2.38), BBS (35.12±4.61 vs. 34.68±5.42) and BI (40.00±10.32 vs. 37.18±7.73). Between the groups comparison of pre post values showed no significance with FMA-LE (p=0.09), BBS (p=0.80) and BI (p=0.39) respectively. Conclusion: Though either groups had significant improvement (pre to post intervention), none of them were superior to other in lower extremity motor recovery and balance among acute stroke subjects. We conclude that eclectic approach is an effective treatment irrespective of NMES or MT as an adjunct.

Keywords: balance, motor recovery, mirror therapy, neuromuscular electrical stimulation, stroke

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Authors: Brajevic-gizdic Igna, Vuletic Gorka

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Introduction: Research in opiate addiction is increasingly indicating the importance of substitution therapy in opiate addicts. Opiate addiction is a chronic relapsing disease that includes craving as a criterion. Craving has been considered a predictor of a relapse, which is defined as a strong desire with an excessive need to take a substance. The study aimed to measure the intensity of craving using the VAS (visual analog scale) in opioid addicts taking the Opioid Substitution Therapy (OST). Method: The total sample compromised of 30 participants in outpatient treatment. Two groups of opiate addicts were considered: Methadone-maintenance and buprenorphine-maintenance addicts. The participants completed the survey questionnaire during the outpatient treatment. Results: The results indicated high levels of cravings in patients during the treatment on OST, which is considered an important destabilization factor in abstinence. Thus, the use of methadone/buprenorphine dose should be considered. Conclusion: These findings provided an objective measurement of methadone /buprenorphine dosage and therapy options. The underdoes of OST can put patients at high risk of relapse, resulting in high levels of craving. Thus, when determining the therapeutic dose of OST, it is crucial to consider patients´ craving. This would achieve stabilization more quickly and avoid relapse in abstinence. Subjective physician assessment and patient’s statement are the main criteria to determine OST dosage. Future studies should use larger sample sizes and focus on the importance of intensity craving measurement on OST to objectify methadone /buprenorphine dosage.

Keywords: abstinence, addicts, methadone, OST, quality of life

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Authors: Sabrine Ammar, Mohamed Tahar Bhiri

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Automatic planning has a de facto standard language called Planning Domain Definition Language (PDDL) for describing planning problems. It aims to formalize the planning problems described by the concept of state space. PDDL-related dynamic analysis tools, namely planners and validators, are insufficient for verifying and validating PDDL descriptions. Indeed, these tools made it possible to detect errors a posteriori by means of test activity. In this paper, we recommend a formal approach coupling the two languages Event-B and PDDL, for automatic planning. Event-B is used for formal modeling by stepwise refinement with mathematical proofs of planning problems. Thus, this paper proposes a refinement strategy allowing to obtain reliable PDDL descriptions from an ultimate Event-B model correct by construction. The ultimate Event-B model, correct by construction which is supposed to be translatable into PDDL, is automatically translated into PDDL using our MDE Event-B2PDDL tool.

Keywords: code generation, event-b, PDDL, refinement strategy, translation rules

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Authors: G. Kloudova, S. Kozlova, M. Stehlik

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Pilots are operating in a high-risk environment rich in potential stressors, which negatively affect aviation safety and the mental health of pilots. In the research conducted, the pilots were offered mental training biofeedback therapy. Biofeedback is an objective tool to measure physiological responses to stress. After only six sessions, all of the pilots tested showed significant differences between their initial condition and their condition after therapy. The biggest improvement was found in decreased heart rate (in 83.3% of tested pilots) and respiration rate (66.7%), which are the best indicators of anxiety states and panic attacks. To incorporate all of the variables, we correlated the measured physiological state of the pilots with their personality traits. Surprisingly, we found a high correlation with peripheral temperature and confidence (0.98) and with heart rate and aggressiveness (0.97). A retest made after a one-year interval showed that in majority of the subjects tested their acquired self-regulation ability had been internalized.

Keywords: aviation, biofeedback, mental workload, performance psychology

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Authors: Modi Alsubaie, Willem Kuyken, Rebecca Abbott, Barnaby Dunn, Chris Dickens, Tina Keil, William Henley

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Background: Recently, there has been an increased interest in studying the effects of mindfulness-based interventions for people with psychological and physical problems. However, the mechanisms of action in these interventions that lead to beneficial physical and psychological outcomes have yet to be clearly identified. Purpose: The aim of this paper is to review, systematically, the evidence to date on the mechanisms of action in mindfulness interventions in populations with physical and/or psychological conditions. Method: Searches of seven databases (PsycINFO, Medline (Ovid), Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, AMED, ClinicalTrials.gov) were undertaken in June 2014 and July 2015. We evaluated to what extent the studies we identified met the criteria suggested by Kazdin for establishing mechanisms of action within a psychological treatment (2007, 2009). Results: We identified four trials examining mechanisms of mindfulness interventions in those with comorbid psychological and physical health problems and 14 in those with psychological conditions. These studies examined a diverse range of potential mechanisms, including mindfulness and rumination. Of these candidate mechanisms, the most consistent finding was that greater self-reported change in mindfulness mediated superior clinical outcomes. However, very few studies fully met the Kazdin criteria for examining treatment mechanisms. Conclusion: There was evidence that global changes in mindfulness are linked to better outcomes. This evidence pertained more to interventions targeting psychological rather than physical health conditions. While there is promising evidence that MBCT/MBSR intervention effects are mediated by hypothesised mechanisms, there is a lack of methodological rigour in the field of testing mechanisms of action for both MBCT and MBSR, which precludes definitive conclusions.

Keywords: MBCT, MBSR, mechanisms, physical conditions, psychological conditions, systematic review

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Authors: Namdeo Jadhav, Nitin Salunkhe

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Currently, sericin is being treated as waste of sericulture industry, especially at reeling process. Looking at prospective physicochemical properties, an attempt has been made to explore pharmaceutical applications of sericin waste in fabrication of medicated solid dispersions. Solid dispersions (SDs) of poorly soluble drugs (Lornoxicam, Meloxicam & Felodipine) were prepared by spray drying, solvent evaporation, ball milling and physical kneading in mass ratio of drug: sericin (1:0.5, 1:1, 1:1.5, 1:2, 1:2.5 and 1:3 w/w) and were investigated by solubility, ATR-FTIR, XRD and DSC, micromeritics and tablettability, surface morphology and in-vitro dissolution. It has been observed that sericin improves solubility of drugs by 8 to 10 times compared to pure drugs. The presence of hydrogen bonding between drugs and sericin was confirmed from the ATR-FTIR spectra. Amongst these methods, spray dried (1:2 w/w) SDs showed fully amorphous state representing molecularly distributed drug as confirmed from XRD and DSC study. Spray dried meloxicam SDs showed better compressibility and compactibility. The microphotograph of spray dried batches of lornoxicam (SDLX) and meloxicam SDs (SDMX) showed bowl shaped, and bowl plus spherical particles respectively, while spray dried felodipine SDs (SDFL) showed spherical shape. The SDLX, SDMX and SDFL (1:2 w/w) displayed better dissolution performance than other methods. Conclusively, hydrophilic matrix of sericin can be used to deliver poor water soluble drugs and its aerodynamic shape may show a great potential for various drug deliveries. If established as pharmaceutical excipient, sericin holds a potential to revolutionise economics of pharmaceutical industry, and sericulture farming, especially of Asian countries.

Keywords: biosericin, poorly soluble drugs, solid dispersion, solubility and dissolution improvement

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Authors: Leslie M. Gutman

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Conduct problems (CP) represent a major dilemma, with wide-ranging and long-lasting individual and societal impacts. Children experience heterogeneous patterns of conduct problems; based on the age of onset, developmental course and related risk factors from around age 3. Early childhood represents a potential window for intervention efforts aimed at changing the trajectory of early starting conduct problems. Using the UK Millennium Cohort Study (n = 17,206 children), this study (a) identifies trajectories of conduct problems from ages 3 to 14 years and (b) assesses the cumulative and interactive effects of individual, family and socioeconomic risk factors from ages 9 months to 14 years. The same factors according to three domains were assessed, including child (i.e., low verbal ability, hyperactivity/inattention, peer problems, emotional problems), family (i.e., single families, parental poor physical and mental health, large family size) and socioeconomic (i.e., low family income, low parental education, unemployment, social housing). A cumulative risk score for the child, family, and socioeconomic domains at each age was calculated. It was then examined how the cumulative risk scores explain variation in the trajectories of conduct problems. Lastly, interactive effects among the different domains of cumulative risk were tested. Using group-based trajectory modeling, four distinct trajectories were found including a ‘low’ problem group and three groups showing childhood-onset conduct problems: ‘school-age onset’; ‘early-onset, desisting’; and ‘early-onset, persisting’. The ‘low’ group (57% of the sample) showed a low probability of conducts problems, close to zero, from 3 to 14 years. The ‘early-onset, desisting’ group (23% of the sample) demonstrated a moderate probability of CP in early childhood, with a decline from 3 to 5 years and a low probability thereafter. The ‘early-onset, persistent’ group (8%) followed a high probability of conduct problems, which declined from 11 years but was close to 70% at 14 years. In the ‘school-age onset’ group, 12% of the sample showed a moderate probability of conduct problems from 3 and 5 years, with a sharp increase by 7 years, increasing to 50% at 14 years. In terms of individual risk, all factors increased the likelihood of being in the childhood-onset groups compared to the ‘low’ group. For cumulative risk, the socioeconomic domain at 9 months and 3 years, the family domain at all ages except 14 years and child domain at all ages were found to differentiate childhood-onset groups from the ‘low’ group. Cumulative risk at 9 months and 3 years did not differentiate between the ‘school-onset’ group and ‘low’ group. Significant interactions were found between the domains for the ‘early-onset, desisting group’ suggesting that low levels of risk in one domain may buffer the effects of high risk in another domain. The implications of these findings for preventive interventions will be highlighted.

Keywords: conduct problems, cumulative risk, developmental trajectories, early childhood, adolescence

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Authors: Pamita Awasthi, Kirna, Shilpa Dogra, Manu Vatsal, Ritu Barthwal

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Doxorubicin, also known as adriamycin, is an anthracycline class of drug used in cancer chemotherapy. It is used in the treatment of non-Hodgkin’s lymphoma, multiple myeloma, acute leukemias, breast cancer, lung cancer, endometrium cancer and ovary cancers. It functions via intercalating DNA and ultimately killing cancer cells. The major side effects of doxorubicin are hair loss, myelosuppression, nausea & vomiting, oesophagitis, diarrhoea, heart damage and liver dysfunction. The minor modifications in the structure of compound exhibit large variation in the biological activity, has prompted us to carry out the synthesis of sulfonamide derivatives. Sulfonamide is an important feature with broad spectrum of biological activity such as antiviral, antifungal, diuretics, anti-inflammatory, antibacterial and anticancer activities. Structure of the synthesized compound N-(1-methyl-2-oxo-2-N-methyl anilino-ethyl)benzene sulfonamide confirmed by proton nuclear magnetic resonance (1H NMR),13C NMR, Mass and FTIR spectroscopic tools to assure the position of all protons and hence stereochemistry of the molecule. Further we have reported the binding potential of synthesized sulfonamide analogues in comparison to doxorubicin drug using Auto Dock 4.2 software. Computational binding energy (B.E.) and inhibitory constant (Ki) has been evaluated for the synthesized compound in comparison of doxorubicin against Poly (dA-dT).Poly (dA-dT) and Poly (dG-dC).Poly (dG-dC) sequences. The in vitro cytotoxic study against human breast cancer cell lines confirms the better anticancer activity of the synthesized compound over currently in use anticancer drug doxorubicin. The IC50 value of the synthesized compound is 7.12 µM where as for doxorubicin is 7.2 µ.

Keywords: Doxorubicin, auto dock, in silco, in vitro

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Authors: Juan Antonio Mondragon Sanchez, Ruben Santamaria

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The DNA G-quadruplex is a four-stranded DNA structure conformed by stacked planes of four base paired guanines (G-quartet). The guanine rich DNA sequences are present in many sites of genomic DNA and can potentially lead to the formation of G-quadruplexes, especially at the 3'-terminus of the human telomeric DNA with many TTAGGG repeats. The formation and stabilization of a G-quadruplex by small ligands at the telomeric region can inhibit the telomerase activity. In turn, the ligands can be used to regulate oncogene expression making the G-quadruplex an attractive target for anticancer therapy. Clearly, the G-quadruplex structured in the telomeric DNA is of fundamental importance for rational drug design. In this context, we investigate two G-quadruplex structures, the first follows from the sequence TTAGGG(TTAGGG)3TT (HUT1), and the second from AAAGGG(TTAGGG)3AA (HUT2), both in a K+ solution. We determine the free energy surfaces of the HUT1 and HUT2 structures and investigate their conformations using replica-exchange metadynamics simulations. The carbonyl-carbonyl distances belonging to different guanines residues are selected as the main collective variables to determine the free energy surfaces. The surfaces exhibit two main local minima, compatible with experiments on the conformational transformations of HUT1 and HUT2 under substitution of the K+ ions by the Na+ ions. The conformational transitions are not observed in short MD simulations without the use of the metadynamics approach. The results of this work should be of help to understand the formation and stability of human telomeric G-quadruplex in environments including the presence of K+ and Na+ ions.

Keywords: g-quadruplex, metadynamics, molecular dynamics, replica-exchange

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Authors: Syed Asif Hassan, Syed Atif Hassan

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Multidrug-resistant Tuberculosis (MDR-TB) is an infection caused by the resistant strains of Mycobacterium tuberculosis that do not respond either to isoniazid or rifampicin, which are the most important anti-TB drugs. The increase in the occurrence of a drug-resistance strain of MTB calls for an intensive search of novel target-based therapeutics. In this context LprG (Rv1411c) a lipoprotein from MTB plays a pivotal role in the immune evasion of Mtb leading to survival and propagation of the bacterium within the host cell. Therefore, a machine learning method will be developed for generating a computational model that could predict for a potential anti LprG activity of the novel antituberculosis compound. The present study will utilize dataset from PubChem database maintained by National Center for Biotechnology Information (NCBI). The dataset involves compounds screened against MTB were categorized as active and inactive based upon PubChem activity score. PowerMV, a molecular descriptor generator, and visualization tool will be used to generate the 2D molecular descriptors for the actives and inactive compounds present in the dataset. The 2D molecular descriptors generated from PowerMV will be used as features. We feed these features into three different classifiers, namely, random forest, a deep neural network, and a recurring neural network, to build separate predictive models and choosing the best performing model based on the accuracy of predicting novel antituberculosis compound with an anti LprG activity. Additionally, the efficacy of predicted active compounds will be screened using SMARTS filter to choose molecule with drug-like features.

Keywords: antituberculosis drug, classifier, machine learning, molecular descriptors, prediction

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Authors: Ana-Katarina Nikich

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Background: The kinesiotaping method is often used in physiotherapy and rehabilitation. The purpose of this study was to evaluate the effectiveness of taping in the rehabilitation process of patients. Materials and methods: The study involved 90 male and female patients (the average age was 40-50 years) with various conditions requiring rehabilitation, such as injuries of the musculoskeletal system, sports injuries and other ailments. All patients were divided into two groups: experimental (n=40) and control (n=50). Both groups received 20 days of standard rehabilitation. In the experimental group, kinesiotaping methods were used, taking into account the individual characteristics of each patient. The control group performed regular exercises and physical therapy, but without using kinesiotape. During the study, physical parameters were monitored, interviews were conducted and the conditions of patients from both groups were compared. Results and discussion: The use of the kinesiotaping method in the rehabilitation process led to a significant improvement in physical parameters and pain reduction in patients. Significant improvement (p <0.005) was observed in all evaluated parameters among the patients of the experimental group. The control group also showed sufficient improvement (p <0.005), but the percentage of the experimental group was higher. As a result of the observation, the patients of the experimental group showed faster and more complete rehabilitation compared to the control group. The use of the kinesiotaping method allows to reduce the load on the damaged areas, improve blood circulation and lymphatic drainage, as well as increase stability and coordination of movements. Conclusions: Kinesiotaping as one of the modern therapeutic methods has shown its effectiveness in the rehabilitation process, contributing to the optimal recovery of patients with various conditions requiring rehabilitation. The use of tapes should be included in a comprehensive rehabilitation program to achieve the best results and reduce recovery time.

Keywords: kinesiotaping, rehabilitation, therapy, pain

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Authors: J. Cabral, C. Barreto Carvalho, C. da Motta, M. Sousa

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Community integration is a construct that an increasing body of research has shown to have a significant impact in well-being and recovery of people with psychiatric problems. However, there are few studies that explore which factors can be associated and predict community integration. Moreover, community integration has been mostly studied in minority groups, and currently literature on the definition and manifestation of community integration in the more general population is scarce. Thus, the current study aims to characterize community integration and explore possible predictor variables in a sample of participants with psychiatric problems (PP, N=183) and a sample of participants from the general population (GP, N=211). Results show that people with psychiatric problems present above average values of community integration, but are significantly lower than their healthy counterparts. It was also possible to observe that community integration does not vary in terms of the socio-demographic characteristics of both groups in this study. Correlation and multiple regression showed that, among several variables that literature present as relevant in the community integration process, only three variables emerged as having the most explanatory value in community integration of both groups: sense of community, basic needs satisfaction and submission. These results also shown that those variables have increased explanatory power in the PP sample, which leads us to emphasize the need to address this issue in future studies and increase the understanding of the factors that can be involved in the promotion of community integration, in order to devise more effective interventions in this field.

Keywords: community integration, mental illness, predictors, psychiatric problems

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Authors: Ahmed. Abdel Bary, Omneya. Khowessah, Mojahed. al-jamrah

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Introduction: The major challenge with the design of oral dosage forms lies with their poor bioavailability. The most frequent causes of low oral bioavailability are attributed to poor solubility and low permeability. The aim of this study was to develop solid nanodispersed tablet formulation of Glimepiride for the enhancement of the solubility and bioavailability. Methodology: Solid nanodispersions of Glimepiride (GMP) were prepared using two different ratios of 2 different carriers, namely; PEG6000, pluronic F127, and by adopting two different techniques, namely; solvent evaporation technique and fusion technique. A full factorial design of 2 3 was adopted to investigate the influence of formulation variables on the prepared nanodispersion properties. The best chosen formula of nanodispersed powder was formulated into tablets by direct compression. The Differential Scanning Calorimetry (DSC) analysis and Fourier Transform Infra-Red (FTIR) analysis were conducted for the thermal behavior and surface structure characterization, respectively. The zeta potential and particle size analysis of the prepared glimepiride nanodispersions was determined. The prepared solid nanodispersions and solid nanodispersed tablets of GMP were evaluated in terms of pre-compression and post-compression parameters, respectively. Results: The DSC and FTIR studies revealed that there was no interaction between GMP and all the excipients used. Based on the resulted values of different pre-compression parameters, the prepared solid nanodispersions powder blends showed poor to excellent flow properties. The resulted values of the other evaluated pre-compression parameters of the prepared solid nanodispersion were within the limits of pharmacopoeia. The drug content of the prepared nanodispersions ranged from 89.6 ± 0.3 % to 99.9± 0.5% with particle size ranged from 111.5 nm to 492.3 nm and the resulted zeta potential (ζ ) values of the prepared GMP-solid nanodispersion formulae (F1-F8) ranged from -8.28±3.62 mV to -78±11.4 mV. The in-vitro dissolution studies of the prepared solid nanodispersed tablets of GMP concluded that GMP- pluronic F127 combinations (F8), exhibited the best extent of drug release, compared to other formulations, and to the marketed product. One way ANOVA for the percent of drug released from the prepared GMP-nanodispersion formulae (F1- F8) after 20 and 60 minutes showed significant differences between the percent of drug released from different GMP-nanodispersed tablet formulae (F1- F8), (P<0.05). Conclusion: Preparation of glimepiride as nanodispersed particles proven to be a promising tool for enhancing the poor solubility of glimepiride.

Keywords: glimepiride, solid Nanodispersion, nanodispersed tablets, poorly water soluble drugs

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Authors: Nilamadhab Mohanty

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It is essential to use message formats that make communication understandable and correct. It is because; the information format can influence consumer decision on the purchase of a product. This study combines information from qualitative inquiry, media trend analysis, eye tracking experiment, and questionnaire data to examine the impact of specific message format and consumer perceived risk on attention to the information and risk retention. We investigated the influence of message framing (goal framing, attribute framing, and mix framing) on consumer memory, study time, and decisional uncertainty while deciding on the purchase of drugs. Furthermore, we explored the impact of consumer perceived risk (associated with the use of the drug, i.e., RISK-AB and perceived risk associated with the non-use of the drug, i.e., RISK-EB) on message format preference. The study used eye-tracking methods to understand the differences in message processing. Findings of the study suggest that the message format influences information processing, and participants' risk perception impacts message format preference. Eye tracking can be used to understand the format differences and design effective advertisements.

Keywords: message framing, consumer perceived risk, advertising, eye tracking

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Authors: P. Thepnarintra, S. Nikorn

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Agricultural machinery industry plays an important role in the industrial development especially the production industry of the country. There has been continuing development responding to the higher demand of the production. However, the problem in agricultural machinery production still exists. Thus, the purpose of this research is to investigate problems on fundamental factors of industry based on the entrepreneurs’ point of view. The focus was on the small and medium size industry receiving a factory license typed number 0660 from the Department of Industrial Works. The investigation was on the comparison between the management of the small and medium size agricultural industry in 3 provinces in the central region of Thailand. Population in this study consisted of 189 company managers or managing directors, of which 101 were from the small size and 88 were from the medium size industry. The data were analyzed to find percentage, arithmetic mean, and standard deviation with independent sample T-test at the statistical significance .05. The results showed that the small and medium size agricultural machinery manufacturers in the central region of Thailand reported high problems in every aspect. When compared the problems on basic factors in running the business, it was found that there was no difference statistically at .05 in managing of the small and medium size agricultural machinery manufacturers. However, there was a statistically significant difference between the small and medium size agricultural machinery manufacturers on the aspect of policy and services of the government. The problems reported by the small and medium size agricultural machinery manufacturers were the services on public tap water and the problem on politic and stability of the country.

Keywords: agricultural machinery, manufacturers, problems, on running the business

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Authors: Siao-Wei Jiang, Boy-Young Hsieh, Ching-Liang Hsieh, Cheng-Yung Lin

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The problems of multiple drug resistance in the pig farming industry have been emphasized in recent years. Diarrhea syndrome is common in weaning piglets and often treated with antibiotics as a feed additive, leading to the rapid spread of antibiotic resistance and posing high health risks to humans. The study aimed to alleviate diarrhea syndrome with traditional herbal medicine, Xiang Sha Liu Jun Zi Tang, whose effects enhanced digestive function. Piglets at 4 weeks old with stool classified to Bristol stool classification type 6 or type 7 were randomly divided into the control group, group A (1% of Xiang Sha Liu Jun Zi Tang) and group B (0.1% Colistin). The piglets were administrated for 7 days, and their weight, feed intake, and stool score were recorded daily before and after the trial. The results showed that the diarrhea index score in group A and group B improved significantly compared to the control group, indicating that Xiang Sha Liu Jun Zi Tang may have the same effect on alleviating diarrhea syndrome as Colistin, and it may be another replacement for antibiotics.

Keywords: pig, diarrhea, herbal medicine, Xiang Sha Liu Jun Zi Tang

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Authors: Anna Kesoyan

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The present paper deals with the syntax-related problems of translation from English into Armenian. Although Syntax is a part of grammar, syntax-related problems of translation are studied separately during the process of translation. Translation from one language to another is widely accepted as a challenging problem. This becomes even more challenging when the source and target languages are widely different in structure and style, as is the case with English and Armenian. Syntax-related problems of translation from English into Armenian are mainly connected with the syntactical structures of these languages, and particularly, with the word order of the sentence. The word order of the sentence of the Armenian language, which is a synthetic language, is usually characterized as “rather free”, and the word order of the English language, which is an analytical language, is characterized “fixed”. The following research examines the main translation means, particularly, syntactical transformations as the translator has to take real steps while trying to solve certain syntax-related problems. Most of the means of translation are based on the transformation of grammatical components of the sentence, without changing the main information of the text. There are several transformations that occur during translation such as word order of the sentence, transformations of certain grammatical constructions like Infinitive participial construction, Nominative with the Infinitive and Elliptical constructions which have been covered in the following research.

Keywords: elliptical constructions, nominative with the infinitive constructions, fixed and free word order, syntactic structures

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Authors: M. A. Abdel-Wahed, Nayera Elmorsi Hassan, Safaa Shafik Imam, Ola G. El-Farghali, Khadija M. Alian

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Low-birth-weight is a challenging public health problem. Aim: to clarify role of zinc on enhancing catch-up growth of low-birth-weight and find out a proposed relationship between zinc effect on growth and the main growth hormone mediator, IGF-1. Methods: Study is a double-blind-randomized-placebo-controlled trial conducted on low-birth-weight-neonates delivered at Ain Shams University Maternity Hospital. It comprised 200 Low-birth-weight-neonates selected from those admitted to NICU. Neonates were randomly allocated into one of the following two groups: group I: low-birth-weight; AGA or SGA on oral zinc therapy at dose of 10 mg/day; group II: Low-birth-weight; AGA or SGA on placebo. Anthropometric measurements were taken including birth weight, length; head, waist, chest, mid-upper arm circumferences, triceps and sub-scapular skin-fold thicknesses. Results: At 12-month-old follow-up visit, mean weight, length; head (HC), waist, chest, mid-upper arm circumferences and triceps; also, infant’s proportions had values ≥ 10th percentile for weight, length and HC were significantly higher among infants of group I when compared to those of group II. Oral zinc therapy was associated with 24.88%, 25.98% and 19.6% higher proportion of values ≥ 10th percentile regarding weight, length and HC at 12-month-old visit, respectively [NNT = 4, 4 and 5, respectively]. Median IGF-1 levels measured at 6 months were significantly higher in group I compared to group II (median (range): 90 (19 – 130) ng/ml vs. 74 (21 – 130) ng/ml, respectively, p=0.023). Conclusion: Oral zinc therapy in low-birth-weight neonates was associated with significantly more catch-up growth at 12-months-old and significantly higher serum IGF-1 at 6-month-old.

Keywords: low-birth-weight, zinc, catch-up growth, neonates

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Authors: Muhammad Tayyab Sohail, Li Jiangfeng

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This study aimed at characterizing land cover dynamics for about three decades in capital city of Pakistan Islamabad. The specific objectives were identifying and map the major land cover types in 1993, 2002 and 2014 and check the reduction of greenery and urbanization rate and its some environments aspects. The study showed that overall grasslands decreased in the prescribed period. The key hotspots of these changes were distributed in all directions of the study area, but at different times. Urbanization is increasing every year in this city but the policies for this number of people are not sufficient to meet their living standard requirements. Apart from it, there is also an impact of urbanization on environmental related problems. Underground water is going down and down, traffic related issue and other associated problems are part of this research. Therefore, policies that integrate restoration and conservation of natural ecosystems with enhancement of agricultural productivity are strongly recommended. This will ensure environmental sustainability and socio-economic well-being in the area. Future research needs to address the problems related to urbanization and need to clarify the problems and solve it on high priority.

Keywords: land, Islamabad, water, urban

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